Pyrethroids are highly potent insecticides of increasing economic importance as replacement compounds in many areas of insect control. Pyrethroids act to compromise nerve impulse transmission in both insects and mammals, but structure-activity relationship in neurotoxicity do not correlate well with structure-insecticidal activity relationships and are therefore an unreliable guide to interpreting the intrinsic specificity of the site of pyrethroid action. Toxicity and pharmacokinetic studies suggest that the action of pyrethroids is mediated by sterospecific reversible binding to an unidentified pyrethroid receptor in the nerve membrane. We have obtained evidence for stereospecific binding in particulate fractions of mouse brain homogenates. The proposed research tests the hypothesis that this stereospecific binding represents a toxicologically significant pyrethroid-receptor interaction. These studies will characterize stereospecific binding of pyrethroids in whole homogenates and centrifugal fractions of nervous tissue from both insects (cockroaches) and mammals (mice) using high specific activity carbon-14 or tritium labeled pyrethroid enantiomers as radioligands. Relative binding affinities for a series of pure pyrethroid isomers representative of known structure-activity relationships will be determined in competitive binding studies. These binding potencies will be compared with estimates of intrinsic potency for the same series of compounds obtained by measuring the steady-state levels of compounds in mouse and cockroach nervous tissue after administration at just-lethal doses. Techniques for the solubilization and purification of stereospecific binding activity will be explored. These studies represent a novel approach to examining the mode of action of pyrethroids; the results will contribute significantly to the understanding of the highly specific interaction between pyrethroids and the nervous system and will aid the rational design of new safe and effective insecticides.